The level of dietary sodium intake is a major determinant of tissue responsiveness to angiotensin II (AII). Animal studies suggest that the circulating AII level acts as the "signal" communicating the state of sodium balance to the target tissues by up- or down-regulating AII receptors. There is now compelling evidence that the adrenal, vascular, and renal respones to AII are altered in subjects with hypertension. We postulate that three abnormalities are related to a defect either in the sodium balance "signal" or in the AII receptor itself. In the proposed studies, we will examine these possibilities through several means. 1) In clinical studies we will investigate the regulation of human AII receptors in normotensive and hypertensive subjects, using the AII receptor we have recently demonstrated on human platelets. 2) We will determine whether the spontaneously hypertensive rat, which demonstrates abnormal adrenal responses to AII, can be used as an animal model of the abnormalities in human hypertension. 3) We will perform comparisons of receptor binding characteristics in rat platelet, adrenal, smooth muscle and renal glomerular AII receptors to determine whether the platelet receptor could represent a mirror for any specific type of AII receptor. 4) We will study the enhancing effect of AII on platelet aggregation to determine whether this action is mediated by platelet AII receptors. Using these approaches, we feel we will clarify the sodium intake/tissue AII responsiveness interaction in normal subjects and characterize the nature of the defects observed in hypertensives. Our results could provide new insight into the mechanisms causing hypertension.